tbuckley/cabot-search huggingface dataset:
Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about<i>UBA1</i>mosaicism
Authors: Jose Manuel Mascaro, Ignasi Rodriguez-Pinto, Gabriela Poza, Anna Mensa-Vilaro, Julian Fernandez-Martin, Luis Caminal-Montero, Gerard Espinosa, Jose Hernández-Rodríguez, Marina Diaz, Joana Rita-Marques, Raimon Sanmarti, Santos Castañeda, Dolores Colunga, Rubén Coto-Hernández, Patricia Fanlo, Jose Ignacio Elejalde, Segundo Bujan, Ignasi Figueras, Francisco Manuel Marco, Mariano Andrés, Silvia Suárez, Andres Gonzalez-Garcia, Xavier Fustà-Novell, Clara Garcia-Belando, Ana Granados, Maria Teresa Fernandez-Figueras, Neus Quilis, Maria Orriols-Caba, Ricardo Gómez de la Torre, Maria Cinta Cid, Georgina Espígol-Frigolé, Alba Alvarez-Abella, Eztizen Labrador, Maria Rozman, Monica Lopez-Guerra, Paola Castillo, Jose R Alamo-Moreno, Eva Gonzalez-Roca, Susana Plaza, Virginia Fabregat, Rocio Lara, Esther F Vicente-Rabaneda, Sonia Tejedor-Vaquero, Giuliana Magri, Nuria Bonet, Manuel Solis-Moruno, Andrea Cerutti, Oscar Fornas, Ferran Casals, Jordi Yagüe, Juan I Aróstegui
Journal: Annals of the Rheumatic Diseases (2023)

The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants.To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines.Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex.Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease.Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.
Symmetric inheritance of parental histones governs epigenome maintenance and embryonic stem cell identity
Authors: Alice Wenger, Alva Biran, Nicolas Alcaraz, Alba Redó-Riveiro, Annika Charlotte Sell, Robert Krautz, Valentin Flury, Nazaret Reverón-Gómez, Victor Solis-Mezarino, Moritz Völker-Albert, Axel Imhof, Robin Andersson, Joshua M. Brickman, Anja Groth
Journal: Nature Genetics (2023)

Modified parental histones are segregated symmetrically to daughter DNA strands during replication and can be inherited through mitosis. How this may sustain the epigenome and cell identity remains unknown. Here we show that transmission of histone-based information during DNA replication maintains epigenome fidelity and embryonic stem cell plasticity. Asymmetric segregation of parental histones H3-H4 in MCM2-2A mutants compromised mitotic inheritance of histone modifications and globally altered the epigenome. This included widespread spurious deposition of repressive modifications, suggesting elevated epigenetic noise. Moreover, H3K9me3 loss at repeats caused derepression and H3K27me3 redistribution across bivalent promoters correlated with misexpression of developmental genes. MCM2-2A mutation challenged dynamic transitions in cellular states across the cell cycle, enhancing naïve pluripotency and reducing lineage priming in G1. Furthermore, developmental competence was diminished, correlating with impaired exit from pluripotency. Collectively, this argues that epigenetic inheritance of histone modifications maintains a correctly balanced and dynamic chromatin landscape able to support mammalian cell differentiation.
Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution
Authors: Alba Rodriguez-Meira, Ruggiero Norfo, Sean Wen, Agathe L. Chédeville, Haseeb Rahman, Jennifer O’Sullivan, Guanlin Wang, Eleni Louka, Warren W. Kretzschmar, Aimee Paterson, Charlotte Brierley, Jean-Edouard Martin, Caroline Demeule, Matthew Bashton, Nikolaos Sousos, Daniela Moralli, Lamia Subha Meem, Joana Carrelha, Bishan Wu, Angela Hamblin, Helene Guermouche, Florence Pasquier, Christophe Marzac, François Girodon, William Vainchenker, Mark Drummond, Claire Harrison, J. Ross Chapman, Isabelle Plo, Sten Eirik W. Jacobsen, Bethan Psaila, Supat Thongjuea, Iléana Antony-Debré, Adam J. Mead
Journal: Nature Genetics (2023)

Abstract Understanding the genetic and nongenetic determinants of tumor protein 53 ( TP53 ) - mutation-driven clonal evolution and subsequent transformation is a crucial step toward the design of rational therapeutic strategies. Here we carry out allelic resolution single-cell multi-omic analysis of hematopoietic stem/progenitor cells (HSPCs) from patients with a myeloproliferative neoplasm who transform to TP53- mutant secondary acute myeloid leukemia (sAML). All patients showed dominant TP53 ‘multihit’ HSPC clones at transformation, with a leukemia stem cell transcriptional signature strongly predictive of adverse outcomes in independent cohorts, across both TP53- mutant and wild-type (WT) AML. Through analysis of serial samples, antecedent TP53 -heterozygous clones and in vivo perturbations, we demonstrate a hitherto unrecognized effect of chronic inflammation, which suppressed TP53 WT HSPCs while enhancing the fitness advantage of TP53- mutant cells and promoted genetic evolution. Our findings will facilitate the development of risk-stratification, early detection and treatment strategies for TP53 -mutant leukemia, and are of broad relevance to other cancer types.
Author Correction: Sensing the DNA-mismatch tolerance of catalytically inactive Cas9 via barcoded DNA nanostructures in solid-state nanopores
Authors: Sarah E. Sandler, Nicole E. Weckman, Sarah Yorke, Akashaditya Das, Kaikai Chen, Richard Gutierrez, Ulrich F. Keyser
Journal: Nature Biomedical Engineering (2023)
Home-based monitoring of ovulation to time frozen embryo transfers in the Netherlands (Antarctica-2): an open-label, nationwide, randomised, non-inferiority trial
Authors: Tjitske Zaat, Jan-Peter de Bruin, Mariëtte Goddijn, Marchien van Baal, Sofie Benneheij, Monique Brandes, Frank Broekmans, Astrid Cantineau, Ben Cohlen, Jeroen van Disseldorp, Susanne Gielen, Eva Groenewoud, Arne van Heusden, Eugenie Kaaijk, Carolien Koks, Corry de Koning, Nicole Klijn, Paul van der Linden, Petra Manger, Lobke Moolenaar, Robbert van Oppenraaij, Quirine Pieterse, Jesper Smeenk, Jantien Visser, Madelon van Wely, Femke Mol
Journal: The Lancet (2023)
Gemtuzumab ozogamicin plus standard induction chemotherapy improves outcomes of newly diagnosed intermediate cytogenetic risk acute myeloid leukemia
Authors: Hassan Awada, Mina Abdelmalek, Tara Cronin, Jeffrey Baron, Zakariya Kashour, Farhan Azad, Muhammad Salman Faisal, Mark Faber, Matthew Gravina, Pamela J. Sung, Steven D. Green, Amanda Przespolewski, James E. Thompson, Elizabeth A. Griffiths, Eunice S. Wang
Journal: Blood Cancer Journal (2023)

Gemtuzumab ozogamicin plus standard induction
Identification of multidrug chemoresistant genes in head and neck squamous cell carcinoma cells
Authors: Neha Khera, Asvika Soodhalaagunta Rajkumar, Khlood Abdulkader M Alkurdi, Zhiao Liu, Hong Ma, Ahmad Waseem, Muy-Teck Teh
Journal: Molecular Cancer (2023)

Abstract Multidrug resistance renders treatment failure in a large proportion of head and neck squamous cell carcinoma (HNSCC) patients that require multimodal therapy involving chemotherapy in conjunction with surgery and/or radiotherapy. Molecular events conferring chemoresistance remain unclear. Through transcriptome datamining, 28 genes were subjected to pharmacological and siRNA rescue functional assays on 12 strains of chemoresistant cell lines each against cisplatin, 5-fluorouracil (5FU), paclitaxel (PTX) and docetaxel (DTX). Ten multidrug chemoresistance genes (TOP2A, DNMT1, INHBA, CXCL8, NEK2, FOXO6, VIM, FOXM1B, NR3C1 and BIRC5) were identified. Of these, four genes (TOP2A, DNMT1, INHBA and NEK2) were upregulated in an HNSCC patient cohort (n = 221). Silencing NEK2 abrogated chemoresistance in all drug-resistant cell strains. INHBA and TOP2A were found to confer chemoresistance in majority of the drug-resistant cell strains whereas DNMT1 showed heterogeneous results. Pan-cancer Kaplan-Meier survival analysis on 21 human cancer types revealed significant prognostic values for INHBA and NEK2 in at least 16 cancer types. Drug library screens identified two compounds (Sirodesmin A and Carfilzomib) targeting both INHBA and NEK2 and re-sensitised cisplatin-resistant cells. We have provided the first evidence for NEK2 and INHBA in conferring chemoresistance in HNSCC cells and siRNA gene silencing of either gene abrogated multidrug chemoresistance. The two existing compounds could be repurposed to counteract cisplatin chemoresistance in HNSCC. This finding may lead to novel personalised biomarker-linked therapeutics that can prevent and/or abrogate chemoresistance in HNSCC and other tumour types with elevated NEK2 and INHBA expression. Further investigation is necessary to delineate their signalling mechanisms in tumour chemoresistance.
Global prevalence of cefiderocol non-susceptibility in Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia: a systematic review and meta-analysis
Authors: Stamatis Karakonstantis, Maria Rousaki, Loukia Vassilopoulou, Evangelos I. Kritsotakis
Journal: Clinical Microbiology and Infection (2023)
Surgical excision versus topical 5% 5-fluorouracil and photodynamic therapy in treatment of Bowen's disease: A multicenter randomized controlled trial
Authors: Shima Ahmady, Patty J. Nelemans, Nicole W.J. Kelleners-Smeets, Aimee H.M.M. Arits, Michette J.M. de Rooij, Janneke P.H.M. Kessels, Brigitte A.B. Essers, Klara Mosterd
Journal: Journal of the American Academy of Dermatology (2023)

Randomized controlled trials comparing the effectiveness of 5-fluorouracil cream, methylaminolevulinate photodynamic therapy (MAL-PDT) and surgical excision in patients with Bowen's disease are lacking.
Reply to: “Short-term activation of PERK alleviates the progression of experimental non-alcoholic steatohepatitis”
Authors: Qi Wang, Qingfa Bu, Haoming Zhou, Ling Lu
Journal: Journal of Hepatology (2023)

We thank Professor Li and his colleagues for their interest in our article "Role of XBP1 in regulating the progression of non-alcoholic steatohepatitis". Our study suggested that XBP1 signaling is upregulated during the natural history of non-alcoholic steatohepatitis (NASH), and pharmacological inhibition of XBP1 can alleviate the progression of NASH.1
Baseline immunophenotypic profile of bone marrow leukemia cells in acute myeloid leukemia with nucleophosmin-1 gene mutation: a EuroFlow study
Authors: Sergio Matarraz, Pilar Leoz, Ana Yeguas-Bermejo, Vincent van der Velden, Anne E. Bras, Jose I. Sánchez Gallego, Quentin Lecrevisse, Rosa Ayala-Bueno, Cristina Teodosio, Ignacio Criado, María González-González, Juan Flores-Montero, Alejandro Avendaño, María B. Vidriales, María C. Chillón, Teresa González, Ramón García-Sanz, María I. Prieto Conde, Neus Villamor, Laura Magnano, Enrique Colado, Paula Fernández, Edwin Sonneveld, Jan Philippé, Michaela Reiterová, Juan C. Caballero Berrocal, Francisco J. Diaz-Gálvez, Fernando Ramos, Julio Dávila Valls, Raquel Manjón Sánchez, Jackeline Solano Tovar, Xavier Calvo, Luis García Alonso, Leonor Arenillas, Sara Alonso, Ariana Fonseca, Covadonga Quirós Caso, Jacques J. M. van Dongen, Alberto Orfao
Journal: Blood Cancer Journal (2023)
Mechanisms and pathophysiology of SARS-CoV-2 infection of the adipose tissue
Authors: Jill Moser, Marloes Emous, Peter Heeringa, Izabela A. Rodenhuis-Zybert
Journal: Trends in Endocrinology and Metabolism (2023)

Obesity is an independent risk factor for severe COVID-19, yet there remains a lack of consensus on the mechanisms underlying this relationship. A hypothesis that has garnered considerable attention suggests that SARS-CoV-2 disrupts adipose tissue function, either through direct infection or by indirect mechanisms. Indeed, recent reports have begun to shed some light on the important role that the adipose tissue plays during the acute phase of infection, as well as mediating long-term sequelae. In this review, we examine the evidence of extrapulmonary dissemination of SARS-CoV-2 to the adipose tissue. We discuss the mechanisms, acute and long-term implications, and possible management strategies to limit or ameliorate severe disease and long-term metabolic disturbances.
Revealing the developmental origin and lineage predilection of neural progenitors within human bone marrow via single-cell analysis: implications for regenerative medicine
Authors: Zhang Changmeng, Wang Hongfei, Martin Chi-Hang Cheung, Ying-Shing Chan, Graham Ka-Hon Shea
Journal: Genome Medicine (2023)

Human bone marrow stromal cells (BMSCs) are an easily accessible and expandable progenitor population with the capacity to generate neural cell types in addition to mesoderm. Lineage tracing studies in transgenic animals have indicated Nestin + BMSCs to be descended from the truncal neural crest. Single-cell analysis provides a means to identify the developmental origin and identity of human BMSC-derived neural progenitors when lineage tracing remains infeasible. This is a prerequisite towards translational application.We attained transcriptomic profiles of embryonic long bone, adult human bone marrow, cultured BMSCs and BMSC-derived neurospheres. Integrated scRNAseq analysis was supplemented by characterization of cells during culture expansion and following provision of growth factors and signalling agonists to bias lineage.Reconstructed pseudotime upon the integrated dataset indicated distinct neural and osteogenic differentiation trajectories. The starting state towards the neural differentiation trajectory consisted of Nestin + /MKI67 + BMSCs, which could also be diverted towards the osteogenic trajectory via a branch point. Nestin + /PDGFRA + BMSCs responded to neurosphere culture conditions to generate a subpopulation of cells with a neuronal phenotype according to marker expression and gene ontogeny analysis that occupied the end state along the neural differentiation trajectory. Reconstructed pseudotime also revealed an upregulation of BMP4 expression during culture of BMSC-neurospheres. This provided the rationale for culture supplementation with the BMP signalling agonist SB4, which directed progenitors to upregulate Pax6 and downregulate Nestin.This study suggested BMSCs originating from truncal neural crest to be the source of cells within long bone marrow possessing neural differentiation potential. Unravelling the transcriptomic dynamics of BMSC-derived neural progenitors promises to enhance differentiation efficiency and safety towards clinical application in cell therapy and disease modelling.
Outcomes Assessments of Sleeve Gastrectomy in a Diet-Induced Non-Alcoholic Steatohepatitis Rats
Authors: Zubaidah Nor Hanipah, Abolfathi Mohammad, Afshin Nazari, Barakatun-Nisak Mohd-Yusof, Ebrahim Falahi, Loqman Mohamad Yusof, Mahtab Zynivand, Mohd Redzwan Sabran, Mohsen Gheitasvand, Omid Ali Adeli, Zubaidah Nor Hanipah
Journal: International Journal of Surgery (2023)

Background: Sleeve gastrectomy (SG) is a valuable procedure in treating or improving obesity, the risk factor of Nonalcoholic Steatohepatitis (NASH). This study aimed to investigate the 12-week outcomes of SG in NASH-induced sprague-dawley rats. Methods: A 12-week high-fat diet-induced male sprague-dawley rat model of NASH (n=24; 6 weeks of age) was randomized into three groups; Sleeve gastrectomy (SG; n=8), Sham Surgery (SS; n=8), and Control (C; n=8). The SG and SS groups underwent surgery in week 12. Results: After 12 weeks of surgical intervention, rats in the SG group had significant weight reduction -16.5% (p &lt; 0.001) but weight increment was seen in the SS and C groups; +1.9 % (p&gt;0.05) and +10.0% (p&lt;0.001), respectively. The SG group showed significantly lower serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as compared to the SS and C groups (p&lt; 0.05). The serum levels of lipid profiles, inflammatory parameters and hepatic antioxidant capacities in the SG group were comparable to the SS group (p&gt;0.05). In 24 weeks, the harvested livers showed no significant differences between the degrees of steatosis, ballooning, inflammation, and NAS in the SG group as compared to the SS groups (p&gt;0.05). Conclusion: SG showed significant weight loss and liver function improvement with no improvement of liver histology, hepatic antioxidant activity, and inflammatory factors, in the NASH-induced animal model after 3 months. A longer-term study is warranted to confirm the benefits of SG in liver histology and other inflammatory factors.
Pervasive under-dominance in gene expression underlying emergent growth trajectories in Arabidopsis thaliana hybrids
Authors: Wei Yuan, Fiona Beitel, Thanvi Srikant, Ilja Bezrukov, Sabine Schäfer, Robin Kraft, Detlef Weigel
Journal: Genome biology (2023)

Complex traits, such as growth and fitness, are typically controlled by a very large number of variants, which can interact in both additive and non-additive fashion. In an attempt to gauge the relative importance of both types of genetic interactions, we turn to hybrids, which provide a facile means for creating many novel allele combinations.We focus on the interaction between alleles of the same locus, i.e., dominance, and perform a transcriptomic study involving 141 random crosses between different accessions of the plant model species Arabidopsis thaliana. Additivity is rare, consistently observed for only about 300 genes enriched for roles in stress response and cell death. Regulatory rare-allele burden affects the expression level of these genes but does not correlate with F1 rosette size. Non-additive, dominant gene expression in F1 hybrids is much more common, with the vast majority of genes (over 90%) being expressed below the parental average. Unlike in the additive genes, regulatory rare-allele burden in the dominant gene set is strongly correlated with F1 rosette size, even though it only mildly covaries with the expression level of these genes.Our study underscores under-dominance as the predominant gene action associated with emergence of rosette growth trajectories in the A. thaliana hybrid model. Our work lays the foundation for understanding molecular mechanisms and evolutionary forces that lead to dominance complementation of rare regulatory alleles.
Correction: Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
Authors: Sonja I. Berndt, Joseph Vijai, Yolanda Benavente, Nicola J. Camp, Alexandra Nieters, Zhaoming Wang, Karin E. Smedby, Geffen Kleinstern, Henrik Hjalgrim, Caroline Besson, Christine F. Skibola, Lindsay M. Morton, Angela R. Brooks-Wilson, Lauren R. Teras, Charles Breeze, Joshua Arias, Hans-Olov Adami, Demetrius Albanes, Kenneth C. Anderson, Stephen M. Ansell, Bryan Bassig, Nikolaus Becker, Parveen Bhatti, Brenda M. Birmann, Paolo Boffetta, Paige M. Bracci, Paul Brennan, Elizabeth E. Brown, Laurie Burdett, Lisa A. Cannon-Albright, Ellen T. Chang, Brian C. H. Chiu, Charles C. Chung, Jacqueline Clavel, Pierluigi Cocco, Graham Colditz, Lucia Conde, David V. Conti, David G. Cox, Karen Curtin, Delphine Casabonne, Immaculata De Vivo, Arjan Diepstra, W. Ryan Diver, Ahmet Dogan, Christopher K. Edlund, Lenka Foretova, Joseph F. Fraumeni, Attilio Gabbas, Hervé Ghesquières, Graham G. Giles, Sally Glaser, Martha Glenn, Bengt Glimelius, Jian Gu, Thomas M. Habermann, Christopher A. Haiman, Corinne Haioun, Jonathan N. Hofmann, Theodore R. Holford, Elizabeth A. Holly, Amy Hutchinson, Aalin Izhar, Rebecca D. Jackson, Ruth F. Jarrett, Rudolph Kaaks, Eleanor Kane, Laurence N. Kolonel, Yinfei Kong, Peter Kraft, Anne Kricker, Annette Lake, Qing Lan, Charles Lawrence, Dalin Li, Mark Liebow, Brian K. Link, Corrado Magnani, Marc Maynadie, James McKay, Mads Melbye, Lucia Miligi, Roger L. Milne, Thierry J. Molina, Alain Monnereau, Rebecca Montalvan, Kari E. North, Anne J. Novak, Kenan Onel, Mark P. Purdue, Kristin A. Rand, Elio Riboli, Jacques Riby, Eve Roman, Gilles Salles, Douglas W. Sborov, Richard K. Severson, Tait D. Shanafelt, Martyn T. Smith, Alexandra Smith, Kevin W. Song, Lei Song, Melissa C. Southey, John J. Spinelli, Anthony Staines, Deborah Stephens, Heather J. Sutherland, Kaitlyn Tkachuk, Carrie A. Thompson, Hervé Tilly, Lesley F. Tinker, Ruth C. Travis, Jenny Turner, Celine M. Vachon, Claire M. Vajdic, Anke Van Den Berg, David J. Van Den Berg, Roel C. H. Vermeulen, Paolo Vineis, Sophia S. Wang, Elisabete Weiderpass, George J. Weiner, Stephanie Weinstein, Nicole Wong Doo, Yuanqing Ye, Meredith Yeager, Kai Yu, Anne Zeleniuch-Jacquotte, Yawei Zhang, Tongzhang Zheng, Elad Ziv, Joshua Sampson, Nilanjan Chatterjee, Kenneth Offit, Wendy Cozen, Xifeng Wu, James R. Cerhan, Stephen J. Chanock, Susan L. Slager, Nathaniel Rothman
Journal: Leukemia (2023)
Optimization of therapeutic antibodies for reduced self-association and non-specific binding via interpretable machine learning
Authors: Emily K. Makowski, Tiexin Wang, Jennifer M. Zupancic, Jie Huang, Lina Wu, John S. Schardt, Anne S. De Groot, Stephanie L. Elkins, William D. Martin, Peter M. Tessier
Journal: Nature Biomedical Engineering (2023)
Kunitz-type protease inhibitor TFPI2 remodels stemness and immunosuppressive tumor microenvironment in glioblastoma
Authors: Lizhi Pang, Madeline Dunterman, Songlin Guo, Fatima Khan, Yang Liu, Erfan Taefi, Atousa Bahrami, Changiz Geula, Wen-Hao Hsu, Craig Horbinski, Charles David James, Peiwen Chen
Journal: Nature Immunology (2023)
Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation
Authors: Qing Wen, Jiaqi Zhou, Congcong Tian, Xinran Li, Guibing Song, Yuan Gao, Yaping Sun, Chiyuan Ma, Sitong Yao, Xiaoyan Liang, Xing Kang, Nan Wang, Yuan Yao, Hongbao Wang, Xiaohuan Liang, Jialin Tang, Steven M. Offer, Xiaohua Lei, Chuanhe Yu, Xiangyu Liu, Zichuan Liu, Zhiquan Wang, Haiyun Gan
Journal: Nature Genetics (2023)